Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001222384 | SCV001394481 | uncertain significance | Neurofibromatosis, type 1 | 2023-06-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 950635). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 24789688). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1251 of the NF1 protein (p.His1251Pro). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |